Referral patterns and outcomes of children who failed Modified Checklist for Autism in Toddlers screening during routine health screening at maternal and child health clinics in the northeast district of Penang: A retrospective cohort study

Abstract Introduction: Autism spectrum disorder (ASD) is a developmental disability that causes significant social, communication and behavioural challenges. The Modified Checklist for Autism in Toddlers (M-CHAT) is a parent-administered screening questionnaire for ASD used at 18 and 36 months of age. This study aimed to determine the outcomes of children who failed M-CHAT screening during routine health screening at maternal and child health clinics in northeast district, Penang and the prevalence of ASD among those with a final diagnosis. Methods: This retrospective cohort study was conducted at 12 maternal and child health clinics. All children who failed M-CHAT screening at 18 and 36 months from January 2017 to December 2021 and received a final diagnosis before 31 March 2022 were recruited. All information required was recorded in a data collection form and analysed using SPSS. Multiple logistic regression was performed to assess the association between the factors and ASD status. Results: Eighty-two children failed M-CHAT screening. Fifty children did not receive a final diagnosis. Among 32 children who received a final diagnosis, 25 were diagnosed with ASD (78.1%). Among the children who underwent M-CHAT screening, the odds of having ASD increased by a factor of 1.2 for every 1-unit increase in age at final diagnosis. Conclusion: In northeast district, Penang, more than half of children who fail M-CHAT screening have no final diagnosis. The specificity of the M-CHAT is 78.1% among children with a final diagnosis of ASD. The age at final diagnosis is positively associated with the diagnosis of ASD.


Introduction
Autism spectrum disorder (ASD) is a developmental disability that causes signi cant social, communication and behavioural challenges.[3][4] In 2020, 1 in 36 children aged 8 years was identi ed to have ASD based on estimates from 11 Autism and Developmental Disabilities Monitoring (ADDM) Network sites across the United States (US; Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah and Wisconsin). 5 No local epidemiological study has yet investigated the prevalence of ASD in Malaysia. 6However, usage of the Modi ed Checklist for Autism in Toddlers (M-CHAT) as a screening tool at health clinics by the Ministry of Health Malaysia shows a prevalence of ASD of 1.6 in 1000 children aged 18-36 months. 6 M-CHAT is a 23-item parent-administered screening questionnaire recommended to be utilised at 18 and 36 months of age to assess the risk for ASD. 1 e speci city of the M-CHAT is reported to be as high as 98%, while the sensitivity, speci city and PPV range from 70% to 92%, from 27% to 43% and from 5.8% to 76%, respectively.2 e M-CHAT has been incorporated into the Malaysian child health record book.Completed questionnaires, either self-administered by parents or guided by nurses, are then scored and recorded in the child health record book.
Children who fail the screening are referred to medical o cers or family medicine specialists at clinics and subsequently to tertiary care settings after assessment.
At present, census on children failing M-CHAT screening is kept by maternal and child health clinic sta in Malaysia.However, to our knowledge, there are no records documenting the outcomes of children who fail M-CHAT screening at primary care facilities after referral to tertiary care centres for diagnosis.Accordingly, this study aimed to determine the outcomes of children who failed M-CHAT screening during routine health screening conducted at 18 and 36 months of age and the prevalence of ASD among those who received a nal diagnosis.We also identi ed possible factors associated with ASD in this cohort.

Methods
is retrospective cohort study was conducted at 12 maternal and child health clinics in the northeast district of Penang in July 2021.
All children who failed M-CHAT screening during routine health screening (Figure 1) at 18 and 36 months of age in the past 5 years (from January 2017 to December 2021) and received a nal diagnosis before 31 March 2022 were included.A data collection form for demographic characteristics, birth and neonatal history, family history of ASD, nal diagnosis and duration from screening to nal diagnosis was used.Data of the children who failed M-CHAT screening during the study period were collected from records derived from yearly census at the 12 maternal and child health clinics (Figure 2).e nal diagnosis of the children who were referred to tertiary care centres was derived from patient case records at a child development clinic, general paediatric clinic and child psychiatry clinic in Penang Hospital.
e data collection forms were numbered from 00 to 82.No names or other identity numbers were used to ensure patient con dentiality.Ethical approval was obtained from the Malaysian Research and Ethics Committee (MREC) with MREC number NMRR ID-22-01251-G4Y.• 25 did not follow through with their referrals to secondary/tertiary centres • 3 did not attend their follow-up appointments at the secondary/tertiary centres after their initial visit • 22 were not referred to a specialist for diagnosis Parental age at the time of delivery, gestational age, birth weight, mode of delivery, maternal illness, neonatal complications, family history of ASD and other comorbidities were also evaluated to identify possible factors associated with ASD.
Categorical variables were summarised as frequencies and percentages, continuous variables with a normal distribution as means and standard deviations (SDs) and continuous variables with a skewed distribution as medians (interquartile ranges).e nal diagnoses were categorised using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.Univariable and multivariable analyses were conducted using logistic regression to test for associations between the variables.Statistical signi cance was considered at a P-value of <0.05.

Results
Of the 93 children who failed M-CHAT screening, four opted to go to private facilities, and seven refused further assessment.Ultimately, 82 children were included in this study.majority of the children (87.8%) did not experience complications during delivery.e neonatal complications identi ed were neurological disorder (8.5%), genetic disorder (2.4%), heart disease (4.9%), neonatal jaundice (14.6%), prematurity (3.7%), global developmental delay (6.1%) and others such as pneumonia, deranged thyroid function, at foot, neonatal hypoglycaemia, ptosis and resolved sepsis (7.3%).
Table 2 presents the ndings of a sub-analysis among the children who received a nal diagnosis of ASD.Of these children, 17 (68%) also had global developmental delay/intellectual impairment; one (4%) had attention-de cit hyperactivity disorder; and seven (28%) did not have any other comorbidities.Among the children with ASD with and without comorbidities, 78.3% and 17.4% had a social communication severity of II and III, respectively, while 30.4% and 69.6% had a restricted repetitive behaviour severity of I and II, respectively.

Discussion
Among the children who failed M-CHAT screening and received a nal diagnosis in this study, 78.1% were diagnosed with ASD. e M-CHAT has been proven to have a high speci city of 98%, 6 as also observed in this study.Accordingly, the M-CHAT is an appropriate and simple screening tool to be used in primary care settings to identify children at risk of ASD.
In the present study, there was a positive association between age at nal diagnosis and diagnosis of ASD.
is nding is consistent with that of a study conducted in Toronto in 2015, where many siblings of children with ASD were not diagnosed with ASD during M-CHAT screening at 18 months of age but were diagnosed at 36 months of age. 7A full diagnostic evaluation at 18 months of age may not be able to identify high-risk children who later receive a diagnosis of ASD owing to the variability in the symptom pro le. 7,8e American Academy of Pediatrics recommends that all children be screened for ASD during child visits at 18, 24 and 36 months of age and when a parent expresses concern that ASD may be missed during earlier child health visits. 4duration from the nal diagnosis to screening in this study was around 13 months, and the age of the children who received their nal diagnosis was 3 years (average=36.5months).Similarly, a study performed in the US showed that the average age at diagnosis was 33.8 months (SD=9.7;range=18-56 months).Conversely, a study conducted in Norway demonstrated that the median age at diagnosis was 4 years, 9 but many children presented with symptoms much earlier at around 18 months of age.10,11 e metaanalysis conducted in 2020 by van 't Hof et al. in the Netherlands to evaluate the average age at diagnosis across studies published from 2012 to 2019 showed a mean age at diagnosis of 43.18 months among children aged 10 years and below.12 Some of the common barriers to early diagnosis often quoted in the literature include a lack of knowledge among parents and healthcare workers, social stigma, dismissal of parents' initial concerns by healthcare providers and access to ASD services.[13][14][15][16][17] Other healthcare factors identi ed are inadequate time for healthcare providers to screen ASD in primary care settings and a lack of trained healthcare providers to perform ASD screening.13 Accordingly, the current practice of M-CHAT screening at 18 and 36 months of age is appropriate.
A US study demonstrated that only 31% of children who failed M-CHAT screening were referred to a specialist, while 65% of them completed their referrals. 18ese ndings are in contrast with the current ndings: ere are di erences in practice between our setting and the setting in the US.In our setting, most primary care doctors refer children who fail their M-CHAT screening owing to the referral system in place and adherence to the preexisting local guidelines on ASD.However, the majority of children in this study did not follow through with their referrals (30.5%) and defaulted after their rst visit (3.7%).e lack of awareness among parents, the failure to follow through on referrals or a combination of the two and other potential factors could have contributed to the lower rates of referral completion.
In the current study, 26.8% of the children who failed their M-CHAT screening were not referred by their primary care doctors to specialists in tertiary care settings for diagnosis.Most children were referred for intervention to occupational and/or speech therapists.However, among these children, those with undiagnosed ASD may miss out on subspecialty assessment and recommendation.Some factors contributing to delay in referrals could be a lack of training and knowledge of the pre-existing referral system.Yearly training on ASD clinical practice guidelines has been provided to healthcare providers in Penang, emphasising the use of M-CHAT as a screening tool across the state and reinforcing the pre-existing referral pathway in place.Owing to the COVID-19 pandemic, all trainings had been temporarily put on hold, resulting in new sta not being able to receive the training needed.From the end of 2022, training has resumed, and future studies can be conducted to evaluate the e ectiveness of the training.In addition to existing training, family medicine specialists with special interest in neurodevelopmental disorders can be provided with options of further subspecialisation or short attachments at tertiary care centres to enable the assessment and management of uncomplicated cases at primary care centres.
A possible measure that can be implemented to address the low rates of referral completion is to the records of patients who are referred.One option that might help is to create a database for children who fail their M-CHAT screening, linking primary and secondary/tertiary healthcare facilities with healthcare sta to ensure that appointments are followed through.
To our knowledge, this study is the rst in Malaysia to focus on the outcomes of children who failed their M-CHAT screening at primary care facilities after referral to tertiary care centres.Universal sampling was used to achieve a good representation of children attending the health clinics, making the results generalisable to the study population.However, there are a few limitations of the study.First, the sample size was small.Accordingly, the statistical analysis was limited.A better statistical analysis could have been performed with a larger sample size to determine the factors associated with ASD.Second, the study was conducted in one out of ve districts in Penang, which is located in an urban area, and the public tertiary referral centre is located in the district involved in this study.e ndings may therefore not be representative of the general population in the community.ree of the districts are located further from the tertiary referral centre (26-50 km), which may a ect the ndings of this study.Future surveys involving a larger population in the entire Penang state could provide further data on the outcomes of children failing M-CHAT screening.
is study o ers a new perspective on the screening and referral processes for children who fail their M-CHAT screening.Substantial e ort is put into early screening and referral at primary healthcare facilities because there is enough evidence to support the idea that children who receive behavioural intervention at a younger age have better developmental outcomes than children who do at an older age. 19,20However, although developmental delays were identi ed early, the nal diagnosis could not be obtained among more than half of the children in the present study.

Conclusion
e M-CHAT is proven to be a good screening tool for early detection of ASD among children.However, many children fail M-CHAT screening but do not receive a con rmatory diagnosis owing to parental and healthcare professional-related factors.
e importance of early diagnosis and intervention should be emphasised among parents.Networking between di erent healthcare facilities is essential to ensure that children referred from primary and secondary care centres complete their consultations with specialists at tertiary care centres.Future similar studies should be conducted in other districts in Penang and other states to obtain more accurate and generalisable data.Barriers to the completion of specialty referrals should also be identi ed, and measures to overcome them should be devised.

Table 1 .
Demographic characteristics of the children who failed Modi ed Checklist for Autism in Toddlers (M-CHAT) screening (N=82).
a Mean (SD); b Median (IQR); c Secondary centre: general paediatric clinic, tertiary centre: child development clinic or child psychiatry clinic *Assisted delivery: vacuum/forceps delivery **Hypertension during pregnancy: pregnant mother with pre-existing hypertension #Mother presenting with signs and symptoms of preeclampsia during pregnancy

Table 2 .
Diagnosis of ASD among the children who failed M-CHAT screening and received a nal diagnosis (n=32).

Table 3
displays the factors associated with ASD in the multiple logistic regression analysis.Among the children who underwent M-CHAT screening, the odds of having ASD increased by a factor of 1.2 for every 1-unit increase in age at nal diagnosis, assuming that all other variables remained constant.

Table 3 .
Multiple logistic regression analysis of the factors associated with ASD (n=32).